1,1'-Carbonyldiimidazole → HCID 131730374, compound

HRID 1963350Notes

Reaction equation

HRID 1963350 reaction equation
[CH3:1][O:2][C:3]([N:5]1[CH2:10][CH2:9][CH:8]([C:11](O)=[O:12])[CH2:7][CH:6]1[CH2:14][C:15]([CH3:23])([C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[CH3:16])=[O:4].[Cl-].[Mg+2].[Cl-].[C:27]([OH:33])(=O)[CH2:28][C:29]([OH:31])=[O:30].[CH2:34]([K])[CH3:35].C(N1C=CN=C1)(N1[CH:43]=[CH:42]N=C1)=O>>[CH2:34]([O:31][C:29](=[O:30])[CH2:28][C:11]([C@@H:8]1[CH2:9][CH2:10][N:5]([C:3]([O:2][CH3:1])=[O:4])[C@@H:6]([CH2:14][C:15]([CH3:23])([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH3:16])[CH2:7]1)=[O:12])[CH3:35].[CH2:42]([O:31][C:29](=[O:30])[CH2:28][C:27]([C@H:8]1[CH2:9][CH2:10][N:5]([C:3]([O:2][CH3:1])=[O:4])[C@@H:6]([CH2:14][C:15]([CH3:16])([C:17]2[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=2)[CH3:23])[CH2:7]1)=[O:33])[CH3:43]

Participants

6

Reactant 4

HCID 682631,1'-CarbonyldiimidazoleHCID 5360315Magnesium ChlorideHCID 66732333HCID 66732333, compound2×HCID 178461627HCID 178461627, compound

Product 2

HCID 131730373HCID 131730373, compoundYield 18%HCID 131730374HCID 131730374, compoundYield 27%

Procedure

The compounds were prepared as described in Example 1, Step 1 starting from crude 1-(methoxycarbonyl)-2-(2-methyl-2-phenylpropyl)piperidine-4-carboxylic acid (7.24 g, 22.7 mmol) (Reference compound 7), magnesium chloride (2.16 g, 22.7 mmol) and ethyl potassium malonate (5.79 g, 34 mmol) and subsequently carbonyldiimidazole (4.41 g, 27.2 mmol) which gave trans-methyl 4-(3-ethoxy-3-oxopropanoyl)-2-(2-methyl-2-phenylpropyl)piperidine-1-carboxylate (1.59 g, 18%) and cis-methyl 4-(3-ethoxy-3-oxopropanoyl)-2-(2-methyl-2-phenylpropyl)piperidine-1-carboxylate (2.38 g, 27%). Trans isomer: 1H NMR (600 MHz, cdcl3) δ 1.20-1.50 (m, 10H), 1.59-1.84 (m, 2H), 1.90 (m, 2H), 2.50-2.89 (m, 2H), 3.16 (m, 2H), 3.58 (m, 4H), 4.17 (m, 4H), 7.06-7.51 (m, 5H). Cis isomer: 1H NMR (600 MHz, cdcl3) δ 1.20-1.41 (m, 10H), 1.57-1.74 (m, 3H), 1.79 (d, 1H), 2.03 (m, 1H), 2.53 (m, 1H), 2.83-3.02 (m, 1H), 3.40 (m, 2H), 3.48-3.68 (m, 4H), 4.03 (m, 1H), 4.12-4.22 (m, 2H), 7.18-7.44 (m, 5H).

Workup

  1. customThe compounds were prepared

Sources & evidence

ORD record
ord-67a9435d4aed42738ba028a0b2113021
Source dataset
uspto-grants-2013_04
Patent number
US08415378B2

Reaction notes

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